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We know how to restore an anti-ageing molecule in our DNA – geneticist

They say age breeds wisdom. But can we grow personally and mature, while staying young and healthy? Can ageing be cured just like any other disease? We asked David Sinclair, professor of genetics at Harvard Medical School.

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Sophie Shevardnadze: David Sinclair, welcome to the show. It's great to have you with us. We've lots to talk about. So you suggest that ageing may be looked at as a disease that can be treated. What makes you think that age is a medical condition rather than the natural course of things?

David Sinclair: Well, thanks, Sophie. Well, ageing is just like every other condition that causes us to be sick and eventually die. We like to think it's natural because it happens to most people. But in 100 years ago, cancer, heart disease, frailty - these are the things that if you lived long enough, you would get. And eventually, we learned how to treat those things. We understood what the basis was. And we're at the same stage with aging. We now have for the first time a fundamental understanding what causes ageing, how to slow it down and even potentially how to how to treat it and reverse the process. And my argument about why we should focus on it is that ageing is the major cause of all of the diseases that we try to stop. And instead of trying to whack them on the head one at a time as they emerge why don't we try to stop us getting to the edge of the cliff in the first place before we drop off?

SS: So if you're right about age being sort of disease, why is today's medicine treating all kinds of diseases that appear in old age and not addressing the old age itself, which may actually be the underlying cause of having a bunch of illnesses when you're 70 plus?

DS: Well, it's completely historical. The medical profession has built itself up to treat things that are already occurring. We call these things diseases. But the only difference between a disease and ageing is that disease happens to less than 50 per cent and ageing happens to 50 per cent or more. And I think that's just... We know that's a completely arbitrary distinction. So it's historical. And in 30 years from now, I'm certain that we'll look back at today and think, why did we ignore this major problem on the planet and why didn't we work on this sooner?

SS: Well, you’re experimenting with NAD+ - that's a molecule, I guess, that takes care of preserving cells (correct me if I'm wrong here) and we lose that molecule as we age, right? So if we take it as a pill, we will stop ageing. What's gonna happen? Have we gotten this right?

DS: Well, we don't know that much yet. What we've been doing as a field is publishing in the world's leading journals about what's driving ageing. But we've also discovered that there are genes in our bodies that protect us from ageing. We call these longevity genes. And there's a set of genes that we work on in my lab at Harvard called the sirtuins. And for those to work effectively to slow ageing and prevent us from getting diseases, they need a molecule called NAD. And you can take supplements that will raise NAD levels in the body. But we only know so far that they work really effectively in animal studies to slow down ageing and give the benefits of exercise and diet without actually having to do that. But we're right in the middle of clinical trials. Some are being run at hospitals at Harvard, some around the world. And we're hopeful in the next year or so we'll have some first true evidence, not just that it's safe, which we know already so far, but that it actually helps to do some of those things that we see in those mouse studies. So it's a very exciting time. And there's hundreds of studies around the world looking at molecules in people to see if we can actually slow down the ageing process.

SS: Well, why hasn't this anti-ageing drug of yours been adopted and mass-produced yet? I mean, I know that you're taking it. Your family is taking it. Nevertheless, it's not approved by the FDA yet. Are there dangers to it that still need to be addressed?

DS: Well, just to be clear, I'm not taking anything that isn't available to the general public. These are supplements, but supplements have a drawback, which is primarily we don't know if they work yet and this is the problem. And so that's why I'm working on these clinical trials that would eventually produce a drug that a doctor could prescribe, knowing that in most people, or at least a number of people, it's proven to work. And initially, it will be prescribed for treating diseases because ageing is not yet a prescribable condition. But why hasn't the world adopted this yet? Well, because we need to prove that these things work. And right now, because things look very promising, many of us, including my family, have decided to take the risk that if we don't do anything, that's even worse, we think. But yeah, it's still a risk. There's still a chance that there could be side effects that we haven't seen yet.

SS: So how long have you been taken it for, if I may ask? And how old are you? I want to see if it's working.

DS: Right. Well, I'm a hundred and three. Honestly,  I wish. So I just turned 50. And so you can be the judge. I don't have any grey hair yet, which is a good sign. 

SS: Yeah, you do look amazing for someone who’s 50. 

DS: Oh, thanks, I appreciate that. And my father is 80 and doing very well. I look even more amazing considering I grew up in Sydney, Australia, sunbathing and getting really burnt and I really should be totally wrinkled. So, so far, so good. But that's not proof that this is working. That said, I'm not an athlete, I don't do a lot of exercise, I wish I had time for that. But my physiology, as far as doctors can tell, is like an athlete. So what I can tell so far is that my father and I are doing well, it’s not hurting us... 

SS: One more time, how long have you been taking it for?

DS: Yeah, well, it depends. So there's a cocktail of a few things that we've been taking based on my lab’s research and some many others around the world. NAD booster molecule I've been taking for a few years now.

SS: I want you to prescribe me what you're taking because I like the way it's looking. So it has no side effects so far, or it hasn't been looked into, or enough time hasn't passed for us to really understand?

DS: Well, every molecule we put in our bodies, even food, has a risk. You know, there are pesticides in food. So it's on a scale of a risk. And we think that these are on the low end of the risk scale because the molecule that I take and my father takes is naturally curing. Our bodies make it. And really, we're just aiming to supplement what we're losing over time and get us back up to a youthful level and the sort of levels that you see in athletes and people who don't eat three meals a day, which we think is also very helpful.

SS: I mean, a lot of people right now are very big on hormone therapy and they're taking this thing called the growth hormone. I don't know how you're looking at that, but does it have like the sort of same effect? From what I can tell elder people after what, like, 45 start to take it and they start to look younger. But it does have bad side effects if you're prone to cancer and all that. But is this like a similar thing to the growth hormone?

DS: Well, it's actually the opposite. What we're talking about is turning on the body's natural defences against diseases and ageing. And this is a long-term effect so that we know that if you calorie-restrict or have intermittent fasting, many studies around the world in people and mostly in animals prevents ageing. And so you can either do that or you can take these molecules. But the growth hormone does the opposite. It actually speeds up your body's growth,  we think, at the expense of turning on longevity pathways that we study. So in my view, growth hormone, while it has some great short-term benefits, you will get stronger, you'll have less chance of falling, which is great for the elderly, in the long run, which is what I'm looking at here in my research, it's like growth hormone would be like burning the candle at both ends instead of putting energy into long-lasting body.

SS: Well, another road you're actually exploring is this partial cellular reprogramming. And that's when, once again, correct me if I'm wrong, you sort of tell old cells in your body that they're young, they're young cells, and they actually start behaving like young cells. How feasible is this method in anti-ageing science?

DS: Well, it's very new. It's similar to when the Wright brothers discovered how to build a glider. And they were just strapping on the engines to see how this thing flies. It's only been around for a couple of years now that we've learned that we can reprogram the body to really be young again, not just temporarily, but we think of a true reset. We found a backup hard drive of youthfulness in cells. And we use a gene therapy currently, and in mice, which is our fields go to organism, we can do things like reprogram the eye. We can put three genes into the eye and turn them on for a few weeks and those old mice will regain their vision. But we don't know the long-term consequences. But it is exciting, at least in principle, that we found that there is a backup copy of youth that we can turn on and reset the function of something as complicated as an eyeball.

SS: Okay, I get you. So, let's say, in principle, if this cellular reprogramming turns out to work, are we saying that ageing is really just a programme built into us, a programme we can actually recode?

DS: Well, yes, we are. So what I think is causing ageing and I've proposed in a book that I just wrote is that ageing is a loss of information, not the genetic information, but the information that tells a cell how to read the genetic information in the same way a DVD would have the information of our genome but it gets scratched as we get older. And what this reprogramming does is it polishes the DVD so we can read the genes correctly. And that's what we're doing. And we see that the cells, in our older bodies, at least in the old mice, those cells still have the information to be young again. We just need to tell them how to read it again.

SS: So David reprogramming our cells, raising the levels of NAD+ molecule - that will help reset the ageing clock, fine, allowing a 60-year-old to feel like 50 or a 40-year-old like 30 and etc. But is it possible to actually stop ageing completely or only slow down?

DS: Well, if you ask me that just two years ago, I would have said there's no way we can stop ageing and we still don't know how to do that. But we do know now how to reprogram cells to be very young again and take the age at least of a mouse’s eye all the way back from one year of age, which is an old eye back to being just a couple of months. So now when you ask me that, I have to say in theory, it's possible that we could reset the body multiple times. Now we've reset an eye once, but we're now testing if we could do it twice, three times and maybe we can reset a 100 times. We don't know just yet, but that's a very exciting prospect that we will be able to have multiple resets within our lifetime.

SS: So, I mean, I know you're not actually promising an eternal life with your technology, but for how long will it be able to extend humans’ lifespan?

DS: Yeah. So I'm a scientist and hopefully a respected one. And my colleagues get very angry when I say things like, “one day we could live to 150”. Now you can't just prove that. But what I can say with some reliability is that we've been on a trend as a species for the last few hundred years, a very linear trend of greatly extending our lifespan, our average lifespan. And if we continue just on that line without any breakthroughs a child born over here in the US today can expect to live to 104 on average. And in Japan, it's 108, 109. So that's very exciting. But what I'm really excited about is if these breakthroughs happen that I'm talking about today, then those numbers could be even greater. And we know that there are many species on the planet, whales, for example, that can live 100 years longer than us. So there's no law that says we all have to die at 80 or 90. And I know that one day we'll figure this out.

SS: What about you? I mean, how long would you want to live if it were completely up to you?

DS: Well, a lot of people think that I'm trying to do this research to save myself, which is not true at all. Anyone who's seen me drive a car knows that I'm not that worried about my own mortality, but I am trying to leave the world a better place than I found it. My grandmother taught me that. She said, humans are capable of terrible things, your job is to do great things. And so that's why I work hard. I mean, I'm in no rush to leave the planet. I don't want to. I  certainly don't want my family members to be in nursing homes and have to be spoon-fed and bathed with a sponge. You don't want that even for your enemies. Well, maybe you do. But what I'm trying to do is to allow people to live longer in a healthier way. And the longer I can live in a healthy way, you know, I wouldn't say no to that.

SS: Well, but here's the way I see that. Today's medicine, you can take care of organs in your body, they grow old or frail, like lungs and liver and kidneys and even the heart. But at the end of the day, it is the brain and then it's a brain failure that is the worst part of ageing, not wrinkles, right? So is the cell therapy you are researching going to keep the brain young and fit for much longer than we're used to?

DS: Yeah, that's the most important question. And if this research didn't protect the brain, I wouldn't work on it. The good news is that everything that my lab and hundreds of other labs around the world have shown is that our approach to medicine, to drugs, is to treat the whole body, to turn on the body's defences, whether it's in the skin to prevent wrinkles, or in the brain to prevent dementia. And so the good news is that this is one of the first approaches to medicine that keeps the entire body young so that we won't end up with a situation that we're heading towards where we're just increasing the number of people with dementia in nursing homes while their hearts beat.

SS: And here's another thing. To be honest, I very much doubt that the anti-ageing treatment you're talking about will ever be widely used by the general public, because even now, the rejuvenation industry caters mostly to the rich and the famous. When the definite anti-ageing treatment is there, will the general public be able to afford all these things?

DS: Yeah, it's a real problem and I'm spending a lot of my time talking to world leaders and to other members of the industry here to make sure that doesn't happen because we could end up with a world where the millionaires and the billionaires have access to this technology. Already they have more access than most people. But we cannot have a world like that. We could end up with a world, a dystopia where rich people's children and even their pets live longer than other people on the planet. But there are drugs, some of which are already on the market for diseases like diabetes. There's a drug we call Metformin or Glucophage, which has signs of longevity and anti-ageing properties. And this drug only costs a few cents per pill. And really, if we were to call ageing a disease today, like the World Health Organization has declared old age as a medical condition, then doctors could prescribe a medicine like Metformin to their patients for very little money and potentially extend their healthy lifespan by five or ten years. So it's happening right now. It's just a matter of knowledge and the regulations.

SS: So you feel like the anti-ageing research has a social responsibility to make sure everyone has access to it?

DS: Oh, yeah, absolutely, that's very important to me.

SS: So is prolonging the life of many people at once maybe some way a dangerous proposition? I mean, seniors outnumbering other generations is already a problem for a lot of countries. If everyone lives to a hundred the pension systems all over the world will just crash, won’t they?

DS: Well, with every generation when we've come up with new medicines people have worried about what's going to happen if we keep people alive for longer. And there's no way we would go back to the 1920s where mothers and children would die for an infected splinter. And so I project and I've done the calculations and written about this, that population is not going to be a problem. We're stabilizing our population. And the healthier people are, the fewer children they have, especially in developing countries. And also the retirement age - what we're going to be doing is shifting the retirement age but in a way that people have the ability to start new careers and take on hobbies and things and community work that they've always wanted to do. And it's a tradeoff. You can't have a longer life and a healthy life without still contributing to society. You can't expect young people to pay for it. So we will have to adjust. But we've been adjusting for the last hundred or so years in a way that I think we'd never go back to the old ways. But no doubt things will change, but I think change for the better, because what we're heading towards is a world where if we don't do this, we're just going to have a huge burden on our economies. Already, Japan and China, increasingly Western and Eastern Europe are suffering under a burden of sick elderly. So why not work to make them a healthy elderly? And then the research says that those elderly people will die much more quickly. And someone, for example, who lives over 100 years old dies within a few weeks and only costs one third the medical costs of someone who lives on an average lifespan.

SS: But also, human outlook on life is rooted in mortality. I mean, we strive to achieve certain things and leave our mark on the world, make children because we're afraid of dying and living this world without a trace, right? We understand that it's going to end so we have so many things to do. What happens if you take away that fear, or at least mitigate it?

DS: Well, let's again look at history. When people lived to 60 instead of to 80 or 90, were their lives better than ours? Did they have a more fulfilled life or do we have a better life? I would argue that the healthy, longer lives that we live mean that we have a much better time on this planet. And that's what future generations will have. And they'll look back at our lives with pity and they'll actually laugh at such a thought that we needed to die young and be fearful of death for us to have meaningful lives, that's a very Protestant and Christian way of looking at the world. And life goes by very quickly. We're not going to live forever. And even if we lived to 120 years, that would go by very quickly. And so, you know, I reject that notion that we need to worry about dying to make life meaningful. In fact, most of us don't even think about dying until it's too late.

SS: So Jeanne Calment , the longest ever living person on Earth, she died at 122. And her relatives are also known to live longer than average. But at the end of the day, is long life also a genetic thing, something that we inherit?

DS: It is partially. So,people who live over 100 typically have a good set of genes, a good set of longevity genes. But we actually know that only 20 per cent of our longevity is genetically predetermined and the rest is up to us, which is enormously empowering. We can live our life with exercise, a bit of hunger in our day is a good thing. And perhaps these supplements will give us the boost so we can all look forward to living over 100. And perhaps one day many of us will make it to that age of 110, perhaps even beyond that.

SS: Oh, David, let's live long enough to see that happen. Thank you so much for that interview. It was wonderful. Good luck with all of your future endeavours. We were talking to David Sinclair, professor of genetics at Harvard Medical School, discovering the causes of ageing and prospects of longevity.

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